Intratemporal vascular tumors: detection with CT and MR imaging

The diagnostic contributions of computed tomography (CT) and magnetic resonance (MR) imaging were compared in 12 patients with benign intratemporal vascular tumors (hemangioma or vascular malformation). The tumors included six in the internal acoustic canal and six in the geniculate ganglion region. Clinical and histologic correlations were made. Two of the six patients with tumors in the internal acoustic canal underwent CT, and both required gas cisternography to show the tumor. Five patients in that group underwent MR imaging, and all five studies showed the tumor. All six patients with geniculate ganglion tumors underwent CT. Results in one study were questionable, and five showed the tumor. Five patients in this group underwent MR imaging, but the MR findings were positive in only two cases. MR imaging should therefore be performed before CT in the evaluation of facial nerve dysfunction, as it demonstrated all tumors in the internal acoustic canal and some in the geniculate ganglion region. If MR findings are negative, CT should then be performed to rule out a possible geniculate ganglion lesion.     

Chronic delta hepatitis in haemophiliacs

The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti-HBs (6/41). Repeated detection of anti-HDV-IgM in 5/41 individuals of this group indicates that circulating HBsAg is not an absolute prerequisite for chronic HDV infection. Overall, chronically active HDV infection was detected more frequently in quiescent than in active chronic HBV infections. Anti-HDV-IgM was not detected in the absence of anti-HDV-IgG antibodies. Anti-HDV-IgG may disappear after resolution of HDV infection, as indicated by the low prevalence (1/42) in such individuals with past HBV infection as well as by loss of anti-HDV-IgG observed in two patients.     

Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed to non-inactivated or inactivated factor concentrates.

BACKGROUND: Until the mandatory introduction of viral inactivation techniques of blood plasma products in the early 1980s many recipients of these products were infected with various viral pathogens. OBJECTIVES: To determine the rate of transmission of GB virus C/hepatitis G virus (GBV-C/HGV) HCV, and HIV through non-virus-inactivated clotting factor concentrates in hemophiliacs, as well as the relation between amount of administered clotting factor and risk for GBV-C/HGV infection. STUDY DESIGN: In this cross-sectional study, we determined retrospectively the rates of infection markers for GBV-C/HGV, HCV, and HIV in a German cohort of hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor concentrates (group A) and in a second group of hemophiliacs who were treated exclusively with virus-inactivated clotting factor (group B). The presence of anti-virus antibodies was determined by ELISA. Viral RNA was detected by RT-PCR. Markers for viral infections were compared to amounts of administered non-virus-inactivated clotting factor. RESULTS: Among hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor the prevalence for GBV-C/HGV, HCV, and HIV was 40.3%, 98.6%, and 56.3%, respectively. In contrast to HIV, the rate of GBV-C/HGV infections did not increase with increasing amounts of consumed non-inactivated clotting factor. Even in the subgroup of heavily treated hemophiliacs the rate of GBV-C/HGV infection markers did not exceed 45%. CONCLUSIONS: The amount of non-virus-inactivated clotting factor is not predictive for the risk of GBV-C/HGV infection in hemophiliacs. Despite repeated parenteral exposure more than 55% of hemophiliacs were not infected with GBV-C/HGV. Our findings indicate a high frequency of host factors preventing parenteral transmission of GBV-C/HGV.     

Identification of families of overlapping polypeptides coded by early "transforming" gene region 1 of human adenovirus type 2.

Antisera against four lines of adenovirus 2-transformed rat cells, including F17 cells which contain only early gene region 1 (map position 1.5–11) (the transforming region), immunoprecipitate major polypeptides of 53,000 (53K) and 15,000 (15K) daltons (Gilead, Y.-H. Jeng, W. S. M. Wold, K. Sugawara, H. M. Rho, M. L. Harter, and M. Green, 1976, Nature (London)264,263–266; W. S. M. Wold and M. Green, 1976, J. Virol.30,297–310). We show here that the 53Ks precipitated by three of these antisera as well as Adl-SV40 induced hamster tumor sera all have identical two-dimensional tryptic [³⁵S]Met-peptide maps. Similarly, all 15Ks precipitated by these antisera have identical maps. Tryptic and chymotryptic maps demonstrate that most if not all of the [³⁵S]Met-peptides of 15K are shared by 53K. Recent tryptic peptide maps (D. Halbert, D. Spector, H. J. Raskas, W. S. M. Wold, and M. Green, unpublished data) prove that the 53K corresponds to a 53K translated in vitro from a 22S RNA derived from map positions 4.5–11 (D. Halbert, D. Spector, and H. J. Raskas, J. Virol., in press). Thus, both the 53K and 15K are coded within map position 4.5–11. Four [³⁵S]Met-labeled polypeptides of 40K–50K, specific to Ad2 early infected human cells, were isolated in O'Farrell-type 2D gels. These polypeptides are coded within map position 1.5-4.5 (D. Halbert, D. Spector, and H. J. Raskas, J. Virol., in press; D. Halbert, D. Spector, H. J. Raskas, W. S. M. Wold, and M. Green, unpublished data). As expected, our tryptic and chymotryptic peptide maps of these four polypeptides indicate no relationship to 53K or 15K. Two of the 40K–50K polypeptides are highly related, the other two are highly related, and all four are partially related. In addition to 53K and 15K, the F17 antiserum precipitated a 28K polypeptide and minor bands of 14K–16K, 18K–20K, and 11K–12K. Tryptic and chymotryptic maps of these polypeptides show that (1)14K–16K and 18K–20K polypeptides are members of the 53K/15K family, (2) 11K–12K polypeptides are related to each other but are unrelated to any other polypeptides, and (3) 28K is unrelated to any other polypeptides. We conclude that early region 1 codes for two (53K/15K family, 40K–50K family) or possibly more (e.g., 11K–12K family) families of polypeptides; the polypeptides included in each family overlap in amino acid sequence and therefore may be translated from overlapping spliced mRNAs. The possible contribution of these polypeptides to the phenotype of Ad2-transformed cells is discussed.     

Neurotologic manifestations of the osteopetroses

Facial nerve paralysis or symptoms of audiovestibular nerve dysfunction may be the first indication of one of the group of bone diseases known as the osteopetroses. We describe three such patients. The pathophysiology of these diseases and the treatment of the resulting symptoms of facial and audiovestibular nerve dysfunction are discussed.     

The evolution of surgical approaches for posterior fossa meningiomas.

OBJECTIVE: To evaluate surgical outcomes for the treatment of posterior fossa meningiomas at the House Ear Clinic from 1987 to 2001. We review our current treatment algorithm and present our postoperative outcomes with attention to facial and auditory neural preservation. STUDY DESIGN: Retrospective review. SETTING: Tertiary care center. PATIENTS: Medical records of 71 patients who underwent posterior fossa meningioma surgery at the House Ear Clinic were reviewed. INTERVENTION: All patients had surgical removal of their meningioma via translabyrinthine, transcochlear, retrosigmoid, extended middle fossa, or combined petrosal approaches by House Ear Clinic neurotologists and neurosurgeons. MAIN OUTCOME MEASURES: Preoperative and postoperative auditory and facial nerve function data were collected. Patient and tumor characteristics including presenting symptoms, completion of tumor resection, and complications secondary to surgery were also recorded. RESULTS: The most common presenting symptoms in this series were otologic, with hearing loss (61%), tinnitus (58%), and imbalance (58%) as the three most common. Gross total resection was achieved in 67 (94%) patients. Hearing-preservation surgery was attempted in 37 (52%) patients (68% via extended middle fossa or combined approach). Twenty-one patients with preoperative Class A hearing had follow-up audiometric data and 18 (86%) had serviceable hearing preserved. Excluding transcochlear craniotomies, 85% of patients had normal facial nerve function postoperatively. Cerebrospinal fluid leak (6%) was the most common complication. CONCLUSIONS: Advances in microsurgical techniques have greatly changed our management of patients with posterior fossa meningiomas. These changes have reduced postoperative morbidity. Specifically, use of the anterior and posterior petrosal approaches has facilitated facial and auditory neural preservation while not compromising the extent of tumor excision.     

Hepatitis C-associated autoimmunity in patients coinfected with HIV.

Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. Methods: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. Results: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). Conclusion: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.     

Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.

Factor IX is a multidomain protein and is the proenzyme of a serine protease, factor IXa, essential for hemostasis. In this report, we describe the molecular basis of hemophilia B (deficiency of factor IX activity) in five patients who have neither deletions nor rearrangements of the factor IX gene. By enzymatic amplification and sequencing of all exons and promoter regions, the following causative mutation in the protease domain of factor IX was identified in each patient: IXSchmallenberg: nucleotide 31,215G----T, Ser365Ile; IXVarel: nucleotide 31,214A----G, Ser365Gly; IXMechtal: nucleotide 31,211G----C, Asp364His; IXDreihacken: nucleotide 30,864G----A, Arg248Gln; and IXMonschau: nucleotide 30,855A----T, Glu245Val. In IXVarel, nucleotide 31,213T was also replaced by C, which results in a silent mutation (GAT----GAC) at Asp-364. Thus, this patient has a double base-pair substitution of TA to CG at nucleotides 31,213 and 31,214 but only a single amino acid change of Ser-365 to Gly. This patient also developed an antibody to factor IX during replacement therapy, which suggests that deletion of the factor IX gene is not necessary for development of the antibody in hemophilia B patients. The levels of plasma factor IX antigen in the patients ranged from 40% to 100% except for IXDreihacken (Arg248Gln), in which case it was approximately 4% of normal. The Ser365Gly and Ser365Ile mutants are nonfunctional because of lack of the active site serine residue. Mutant Asp364His is inactive because it cannot form the hydrogen bond between the carboxylate group of Asp-364 and the alpha-amino group of Val-181 generated after activation. As observed in other homologous serine proteases, this hydrogen bond is essential for maintaining the correct active site conformation in normal factor IXa (IXaN). Purified Arg248Gln had approximately 41% and Glu245Val had approximately 17% of the activity of normal factor IX (IXN) in a partial thromboplastin time (aPTT) assay. In immunodot blot experiments, the isolated Glu245Val mutant did and the Arg248Gln mutant did not bind to an anti-IXN monoclonal antibody that has been shown previously to inhibit the interaction of factor VIIIa with factor IXaN. We have recently shown that a high-affinity calcium binding site exists in the protease domain of IXN; among the proposed Ca(2+)-binding ligands is the carboxyl group of Glu-245. Further, a part of the epitope for the above antibody was shown to be contained in the 231 to 265 residue segment of factor IX.(ABSTRACT TRUNCATED AT 400 WORDS)     

HCV—specific cytokine induction in monocytes of patients with different oputcomes of hepatitis C

AIM：Cytokine release by macrophages critically determines the type of immune response to an antigen Therefore.we studied hepatitis C virus (HCV0-Specific induction of interleukins-1β,-10,-12(IL-1β,il-10,IL-12),and tumor necrosis factor-α(TNF-α) in monocytes.METHODS:Intracellular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear cells with recombinant core,NS3,NS4 NS5a and NS5b proteins .RESULTS:Patients with HCV viremia revealed greater spontaneous exprssion of IL-1β,TNF-α,and IL-10,Furthermore,greater than twofold higher IL-10 epression was induced by the HCV antigens in chronic hepatitis C than in the other two groups (P&lt;0.05) In contrast,neither IL-12 noir TNF-α was induced preferentially.CONCLUSION:In chonic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines,This may contribute to persistent viral replication.